Durai, Prasannavenkatesh Ko, Young-Joon Kim, Jin-Chul Pan, Cheol-Ho Park, Keunwan 2024-01-19T15:32:37Z 2024-01-19T15:32:37Z 2021-08-31 2021-02 1420-3049 https://pubs.kist.re.kr/handle/201004/117495 Tyrosinase is an enzyme that plays a crucial role in the melanogenesis of humans and the browning of food products. Thus, tyrosinase inhibitors that are useful to the cosmetic and food industries are required. In this study, we have used evolutionary chemical binding similarity (ECBS) to screen a virtual chemical database for human tyrosinase, which resulted in seven potential tyrosinase inhibitors confirmed through the tyrosinase inhibition assay. The tyrosinase inhibition percentage for three of the new actives was over 90% compared to 61.9% of kojic acid. From the structural analysis through pharmacophore modeling and molecular docking with the human tyrosinase model, the pi-pi interaction of tyrosinase inhibitors with conserved His367 and the polar interactions with Asn364, Glu345, and Glu203 were found to be essential for tyrosinase-ligand interactions. The pharmacophore features and the docking models showed high consistency, revealing the possible essential binding interactions of inhibitors to human tyrosinase. We have also presented the activity cliff analysis that successfully revealed the chemical features related to substantial activity changes found in the new tyrosinase inhibitors. The newly identified inhibitors and their structure-activity relationships presented here will help to identify or design new human tyrosinase inhibitors. English MDPI Identification of Tyrosinase Inhibitors and Their Structure-Activity Relationships via Evolutionary Chemical Binding Similarity and Structure-Based Methods Article 10.3390/molecules26030566 1 MOLECULES, v.26, no.3 MOLECULES 26 3 scie scopus 000615456500001 2-s2.0-85100574318 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article evolutionary chemical binding similarity ECBS tyrosinase inhibitors activity cliffs pharmacophore molecular docking